Steps of metabolism of protein in the body

1. Protein Metabolism
By
sally Mohamed Aboelsayed

2. Learning
objects
• Nitrogen balance.
• Amino acids pool.
• Catabolism of amino acids.

3. Nitrogen balance
o Nitrogen balance: the relationship between
the nitrogen intake (in the form of protein)
and nitrogen excretion.
o Nitrogen equilibrium: the rate of body protein
synthesis is equal to the rate of degradation
o Positive nitrogen balance: nitrogen intake >
nitrogen excretion.
o In growing infants and pregnant women.
o Negative nitrogen balance: nitrogen
excretion> nitrogen intake.
o During major injury and trauma & in
advanced cancer. If this situation is
prolonged, it will lead to death.

4. Amino acid
pool

5. Amino acid
pool

6. Amino acids
catabolism
stages
3. Disposal (catabolism) of the remaining
carbon skeleton of amino acid to carbon
dioxide and water by reactions of citric acid
cycle.
2. Disposal of ammonia in the form of urea in
the liver by reactions of the urea cycle.
1. Removal of α-amino group in the form of
ammonia.

7. 1. Removal of α-amino group in
the form of ammonia.

8. Removal of
α-amino group
in the form of
ammonia
I-Transamination by transaminases
enzymes.
II-Deamination (oxidative or
nonoxidative)
a. Oxidative deamination is by glutamate
dehydrogenase or amino acid oxidase.
b. Nonoxidative deamination is by amino acid
dehydratase.

9. Transamination
o The transfer of α-amino group of α-amino acid to an
α-keto acid to form new amino acid and a new keto
acid.
o The enzymes that catalyze these reactions are called
aminotransferases or transaminases.

10. Transamination
o Most transaminases use α-ketoglutarate (α-keto acid)
as a common acceptor of amino groups.
o All transaminases require pyridoxal phosphate (PLP)
as a coenzyme.

11. Transamination
o Most amino acids undergo transamination reaction except
lysine, threonine, proline and hydroxyproline.
o No net loss of amino groups in transamination reactions.
o Transamination reactions are readily reversible, this
permits transaminases to function both in amino acid
catabolism and biosynthesis

12. Transamination
o Some of the most important transaminases
are alanine transaminase (ALT) and
aspartate transaminase (AST).

13. Transamination
Significance
o Provides a mechanism for collecting the
amino groups from many different amino
acids into one common product L-
glutamate.
o This is important because glutamate is the
only amino acid whose α-amino group can
be directly removed at a high rate by
oxidative deamination.

14. Deamination
• The α-amino groups of most amino acids are ultimately
transferred to α ketoglutarate by transamination forming L-
glutamate.
• Then L-glutamate undergoes oxidative deamination by the
action of L-glutamate dehydrogenase, which requires NAD+
or NADP+ as an oxidizing agent .
1) Oxidative deamination by glutamate
dehydrogenase

15. Deamination
Both L- and D-amino acid oxidases occur in the kidneys and
the liver. However, their activities are low.
Amino acid oxidases use auto-oxidizable flavins (FMN or
FAD) as coenzyme, which oxidize amino acids to an α-imino
acid.
2)Oxidative deamination by amino acid oxidases

16. Deamination
α-Imino acid is an unstable compound which decomposes
to the corresponding α-keto acid with release of ammonium
ion. In this reaction, oxygen is reduced to H2O2, which is
later decomposed by catalase.
2)Oxidative deamination by amino acid oxidases

17. 2. Disposal of ammonia in the
form of urea in the liver
(urea cycle).

18. Reactions
1 Formation of Carbamoyl Phosphate.
2 Formation of Citrulline.
3 Formation of Arginosuccinate.
4 Formation of Arginine and Fumarate.
5 Formation of Urea and Ornithine.

19. Urea
cycle

20. Energy
requirement
4 ATPs are consumed in the synthesis of
each molecule of urea .
2 ATP for carbamoyl phosphate
synthesis.
-1 ATP as a source of phosphate
-1 ATP is converted to AMP + PPi.
1 ATP is required to make
arginosuccinate.

21. Significance
Conversion of toxic ammonia into
harmless nontoxic urea.
Disposal of 2 waste products, ammonia
and CO2.
Formation of arginine (semi essential
amino acid).

22. Significance
Regulation of blood pH, which depends
upon the ratio of dissolved CO2.(
H2CO3 to HCO3)
Formation of proline (nonessential
amino acid )from ornithine.
Formation of polyamines (as spermine )
from ornithine.

23. Regulation
 Carbamoyl phosphate synthetase-I is an
allosteric regulatory enzyme of urea cycle,
which is allosterically activated by N-acetyl
glutamate (NAG).
 NAG is synthesized from acetyl-CoA and
glutamate by NAG-synthase to activate CPS-I.
It has no other function.
 Intake of protein rich diet and arginine and
during starvation increase the synthesis of
NAG.

24. Regulation
 Carbamoyl phosphate synthetase-I is
allosterically activated by N-acetyl glutamate
(NAG).
 NAG is synthesized from acetyl-CoA &
glutamate by NAG-synthase .
 NAG synthesis is increased by:
• Intake of protein rich diet.
• Arginine.
• During starvation.

25. Metabolic
Inborn Errors
5 disorders associated with each of the 5
enzymes of urea cycle have been reported.
All defects in urea synthesis result in
hyperammonemia and ammonia intoxication.
Symptoms
• Ammonia intoxication • Protein induced
vomiting
• Intermittent ataxia • Irritability
• Lethargy • Mental retardation.

26. Blood urea
• Normal range of blood urea for a healthy adult
is
20 to 40 mg/dL.
High protein diet shows increase in level of blood
urea concentration.
• In clinical practice, blood urea level is taken as
an indicator of renal function.
•Uremia is used to indicate increased blood urea
levels.

27. 3. Disposal (catabolism) of the
remaining carbon skeleton of amino
acid to carbon dioxide and water by
reactions of citric acid cycle.

28. Catabolism of
the remaining
carbon skeleton
of amino acid
The carbon skeletons of 20 amino acids
are converged into 7 products:
• Pyruvate
• Acetyl-CoA • Acetoacetyl-
CoA
• α-Ketoglutarate • Succinyl-CoA
• Fumarate • Oxaloacetate.

29. Metabolic fate of amino acids carbon skeleton

30. Phenylalanine and tyrosine catabolism